The live smallpox vaccine was a historical first and highly effective vaccine. However, along with high immunogenicity, the vaccinia virus (VACV) caused serious side effects in vaccinees, sometimes with lethal outcomes. Therefore, after global eradication of smallpox, VACV vaccination was stopped. For this reason, most of the human population worldwide lacks specific immunity against not only smallpox, but also other zoonotic orthopoxviruses. Outbreaks of diseases caused by these viruses have increasingly occurred in humans on different continents. However, use of the classical live VACV vaccine for prevention against these diseases is unacceptable because of potential serious side effects, especially in individuals with suppressed immunity or immunodeficiency (e.g., HIV-infected patients). Therefore, highly attenuated VACV variants that preserve their immunogenicity are needed. This review discusses current ideas about the development of a humoral and cellular immune response to orthopoxvirus infection/vaccination and describes genetic engineering approaches that could be utilized to generate safe and highly immunogenic live VACV vaccines.

Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication of smallpox in 1980, strongly recommended to discontinue the vaccination in all countries. This led to the loss of immunity against not only smallpox but also other zoonotic orthopoxvirus infections in humans over the past years. An increasing number of human infections with zoonotic orthopoxviruses and, first of all, monkeypox, force us to reconsider a possible re-emergence of smallpox or a similar disease as a result of natural evolution of these viruses. The review contains a brief analysis of the results of studies on genomic organization and evolution of human pathogenic orthopoxviruses, development of modern methods for diagnosis, vaccination, and chemotherapy of smallpox, monkeypox, and other zoonotic human orthopoxvirus infections.

Human hepatitis B virus (HBV) causes a communicable disease that spreads worldwide and has brought about considerable economic losses due to human mortality and morbidity. HBV fails to reproduce in both cell cultures and laboratory animals; however, it is known that excess virion surface protein named hepatitis B surface antigen (HBsAg) is produced during viral replication and circulates in the blood of carriers as noninfectious particles of 22-nm diameter. It had been shown that purified HBsAg particles induce an efficient systemic immune response after injection. Consequently, subunit HBV vaccines based on HBsAg synthesized in yeasts or mammalian cell culture are currently used. Taking into account that hepatitis B is a sexually transmitted disease, development of a mucosal HBV vaccine would be beneficial. In this article, we analyze the data on development of plant-based HBV vaccines.